Browse Articles

Abstract P2077: The Safety Profile of Inclisiran in Patients with Dyslipidemia : A Systematic Review and Meta-Analysis

Introduction: Inclisiran is a novel drug that employs ribonucleic acid (RNA) interference to lower the levels of the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein. It has demonstrated a significant reduction in LDL cholesterol levels compared to placebo. We aim to comprehensively evaluate the safety of using inclisiran in patients with dyslipidemia and ASCVD or ASCVD risk equivalent. Methods: Four electronic databases of Pubmed/MEDLINE, Web of Science, Embase and ClinicalTrials.gov were searched from inception to May 5th, 2024, to identify relevant randomized controlled trials (RCTs) comparing safety profiles of inclisiran and the control group. The outcomes investigated were all-cause mortality, major adverse cardiovascular events (MACE), injection site adverse events, new onset or worsening type 2 diabetes mellitus (T2DM), and nasopharyngitis. The effect estimates of outcomes were assessed using risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method. Subgroup analysis was performed based on different dosing regimens. Results: The study included 7 RCTs enrolling 4790 patients (age 63.8 ± 9.7 years, 33.2 % females) who received inclisiran. Compared to the control group, inclisiran use did not yield a significant effect on all-cause mortality (RR, 0.92; 95% CI, 0.54 to 1.54; I 2 = 0%), MACE (RR, 0.98; 95% CI, 0.82 to 1.17; I 2 = 0%), nasopharyngitis (RR, 1.10; 95% CI, 0.83 to 1.45; I 2 = 0%) and T2DM (RR, 1.02; 95% CI, 0.85 to 1.21; I 2 = 0%). However, inclisiran use demonstrated a significant increase in injection site adverse events (RR, 7.08; 95% CI, 3.42 to 14.64; I 2 = 27%). Conclusions: Inclisiran use significantly increased injection-site reaction, with no increase in mortality, T2DM, or nasopharyngitis. Further trials are required to assess the safety of inclisiran, particularly the association of the severity of injection site adverse events over longer treatment durations exceeding 540 days.

Abstract P3073: Racial/Ethnic Disparities in the Hypertension Control Cascade Among U.S. Young Adults

Introduction: Treating hypertension in young adulthood can reduce the cumulative burden of elevated BP and prevent end organ damage. Despite marked improvements in from 2000-2010, hypertension prevalence, awareness, treatment, and control rates (the ‘hypertension control cascade’) plateaued among US adults after 2010. No recent study has examined trends in young adult hypertension control across race/ethnicity groups. Objective: We aimed to estimate the prevalence of hypertension control cascade elements by age-group and race/ethnicity in CVD-free U.S. adults, using contemporary data. Methods: Analyses were completed with 2015-March 2020 NHANES data. Survey-weighted logistic regression estimated the odds ratio for race/ethnicity and each element of the hypertension control cascade, adjusting for age and sex. Analyses were completed separately for young and older adults. Finally, we projected the total number of young adults living with hypertension and uncontrolled hypertension by combining prevalence data, the proportion of each age-group that was CVD-free, and population estimates from the U.S. census bureau. Results: Hypertension prevalence was substantially higher for older adults compared to young adults (44% vs 9.7%). Rates of awareness (83% vs 70%), treatment (77% vs 55%), and control (56% vs 43%) were higher for older versus younger adults. Around 9.4M (95% CI: 7.1M-11M) CVD-free young adults have hypertension, of whom, around 5.3M (95% CI: 4.7-6.0M) have uncontrolled hypertension. Compared to Non-Hispanic White (NHW) young adults, Non-Hispanic Black (NHB) counterparts had a significantly elevated likelihood of having hypertension (odd ratio [OR]: 1.04, 95% CI 1.01-1.07). Among those with hypertension, NHB young adults also had significantly lower likelihood of hypertension treatment (OR 0.80, 95% CI: 0.71-0.90) and control (OR 0.77, 95% CI 0.68-0.87). Similarly, Hispanic young adults had significantly lower likelihood of hypertension awareness (OR 0.78, 95% CI: 0.67-0.92), treatment (OR 0.74, 95% CI: 0.64-0.85), and control (OR 0.79, 95% CI: 0.69-0.90). Conclusion: Rates of hypertension control are significantly lower for young adults and especially for those from racial/ethnic minority groups. This likely leads to disparity in later life health outcomes. Unequal hypertension control across racial/ethnic groups in older adulthood may be partly explained by differences in awareness and treatment in young adulthood.

Assessment of health risks of university professors through exposure to BTEX compounds from white board markers

Modulation of the human GlyT1 by clinical drugs and cholesterol

Abstract P1054: Associations between household economic stability and childhood behavioral cardiovascular health: the Young Hearts Study

Background: Household economic stability may alleviate life stressors, allowing children to develop healthy behaviors which in turn will delay the decline of cardiovascular health (CVH) in the life course. Here, we aimed to quantify the associations between household economic stability and behavioral CVH in childhood. Methods: Analyses used data from participants ages 0-18y in the Young Hearts study, an ongoing Chicago-based cohort. Guardians completed surveys on household economic stability and CVH behaviors. Household economic stability encompassed self-reported food security, perceived financial stability (based on difficulty paying for food, heating, or medical care), and having ≥6 months of savings. We calculated behavioral CVH scores by averaging scores on the behavioral components of the AHA Life’s Essential 8 (diet, physical activity, nicotine exposure, and sleep) and body mass index (BMI) score; component scores were 0-100 points each, with higher implying better CVH. Linear regression estimated associations between household economic stability and CVH adjusting for child age, sex, race, ethnicity, insurance, and household income. Results: Of 6,892 included children and adolescents, 47.6% were female, average age was 8.7 [SD 5.5] years, 46.0% were non-Hispanic White, 65.8% were food secure, 50.6% were financially stable, and 19.1% had ≥6 months of savings. Holding household income constant, food security, perceived financial stability, and ≥6 months of savings were associated with a 3.2 (95% CI 2.4, 4.0), 2.3 (1.5, 3.0), and 2.4 (1.7, 3.2) point higher behavioral CVH score, respectively. Additionally, BMI score was higher (more favorable) across all 3 metrics (food security 9.4 [7.1, 11.6]; financial security 10.7 [8.6, 12.8]; ≥6 months of savings 6.9 [4.9, 9.0] points). Conclusion: Household economic stability is associated with more ideal behavioral CVH and BMI in children and adolescents. Policies directed towards improving household financial stability could catalyze improvements in behavioral CVH habits that have long-term cascading impacts on lifetime CVH risk.

Abstract P2109: Sex Differences in the Plasma Metabolome Before and After Exercise Training

Background: Sex differences in metabolites, particularly their changes with exercise training, are largely unknown. We hypothesized that metabolites would not largely differ between males and females at baseline, but that most of the exercised-induced changes in metabolites would be sex-specific. Methods: Plasma metabolites were measured using untargeted LC-MS methods before and after a 20-week exercise intervention in participants from the HERITAGE Family Study (n=671, 56% Female, 35% Black, 17-65 yrs). A total of 810 metabolites were included. Sex differences at baseline were examined using Student t-tests. Paired t-tests were used to examine changes in metabolites with exercise training by sex. Significance was defined as FDR<0.05. Results: At baseline, the levels of 398 plasma metabolites were higher in males, while 155 were higher in females. The most significant sex differences were found for creatine, uric acid, and androsterone 3-glucuronide. Most exercise training changes in the plasma metabolome were sex-specific (74%, Fig 1A ). A majority of the female-specific metabolite changes were in carnitines and LPCs, with the highest individual changes in DG 30:1, CAR 10:2, and ectoine. Most of training changes observed only in males were in TGs, DGs, and PCs, with the greatest individual changes in PE 40:6, adenosine, and TG 54:9 ( Fig 1B ). Conclusions: Most of the plasma metabolites were different between sex groups at baseline, but importantly, a majority of the exercise-induced changes occurred in only males or females. The differential sex response of the plasma metabolome to exercise training observed in this study could represent important sex-specific metabolic pathway responses to an exercise intervention.

Abstract P3117: Association of Body Roundness Index (BRI) with Left Ventricular Mass and Geometry: The Framingham Heart Study

Introduction: Body roundness index (BRI) is a metric of body shape incorporating both girth (waist circumference, WC) and height (HT), where BRI=364.2 – 365.5*SQRT(1- (WC/(π*HT)) 2 ). In contrast to body mass index (BMI) which does not account for body shape, BRI may be better able to identify adiposity. Increased left ventricular mass (LVM) indexed to body size predicts excess cardiovascular morbidity and mortality, but it is not clear whether indexation to HT or powers of HT, or to body surface area (BSA) are optimal. We sought to determine whether there is association between BRI and various methods of LVM indexation. Methods: 1764 members (944 women) of the Framingham Offspring cohort underwent cardiac magnetic resonance (CMR). Participants were divided into sex-specific tertiles of BRI, then a “referent group” without prevalent CVD, wall-motion abnormalities on CMR, or any history of hypertension was identified. We used sex-specific ANCOVA to test for linear trend across BRI tertiles for LVM and LVM indexed to HT, HT 2.7 , BSA, and total body weight (WT). We further investigated two measures of concentricity (“LV geometry”), as high concentricity is associated with excess morbidity. Relative wall thickness (RWT) was LV wall thickness/chamber diameter, Mass-volume ratio (MVR) was LVM/ end-diastolic volume. Results: The proportion of Offspring meeting Referent criteria (N=775, 57% women) decreased with greater BRI for each sex; Table 1. Table 2 shows that LVM and LVM indexed to HT or HT 2.7 increased with greater BRI, significantly for all except LVM in men. LVM/BSA was not different across tertiles of BRI among women, and decreased minimally (by <3g/m 2 ) in men (p=0.049). LVM/WT decreased markedly with higher BRI in both sexes. RWT did not differ across BRI tertiles in men, but increased among women. MVR increased with greater BRI in both sexes (Table 3). Conclusions: LVM indexed to BSA is largely indifferent to BRI, but HT-indexed LVM increases, and LVM/WT decreases with greater BRI category. These results may suggest that HT indexation, which does not account for WT, may be “under adjustment”. However, simply indexing to WT may also be inappropriate, if the allometric relationship between LVM and body mass is dependent on the type of mass (i.e. fat vs non-fat mass). It remains to be determined which method of LVM indexation is best predictive of incident cardiovascular and overall morbidity and mortality.

Effect of lockdown during COVID-19 pandemic on physical endurance among healthy male university students in Wuhan: a retrospective cohort study

Higher temperature sensitivity of forest soil methane oxidation in colder climates

Abstract P1016: Relationships between Sex and In Hospital Outcomes in Patients with Complete Heart Block.

Background: There is a growing body of data to support the presence of sex disparities in outcomes in cardiovascular related hospitalizations. Despite this, there remains a paucity of data on relationships between sex and in-hospital outcomes in cases of Complete Heart Block (CHB). Methods: We examined the 2016-2020 Nationwide Readmission Database (NRD) to identify patients with a principal diagnosis of CHB. Men were used as our control group, while women comprised our cohort. The primary outcome was in-patient mortality. Secondary outcomes included odds of mechanical ventilation use, all cause 30-day readmission, length of stay (LOS) and total hospitalization charges (THC). Multivariate linear and logistic regression models were used to adjust for confounders. Results: Among the patients with CHB (N = 175,257), 45% were Female. A Female sex was associated with higher odds of in-hospital mortality (adjusted OR [aOR] 1.42, 95% CI 1.3 – 1.55, p<0.001) compared to male patients with CHB. Additionally, female sex was associated with a higher likelihood of mechanical ventilation use (aOR 1.1, 95% CI 1.03 – 1.2, p=0.004), all cause 30-day readmission (aOR 1.08, 95% CI 1.03 – 1.13, p=0.004), longer LOS (4.13 days vs 3.86 days, p<0.001) and lower THC ($89,908 vs. $94,590, p=0.002) compared to male patients with CHB. Conclusion: Among patients with CHB, female sex was associated with higher odds of mortality, non-fatal adverse events, and lower resource utilization compared to male patients.

Abstract P2116: Peripheral Artery Disease Identified by Multi-Modalities and Accelerometry-Derived Physical Activity in the community: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction: Lower extremity peripheral artery disease (PAD) causes pain and discomfort with exertion, possibly leading to reduced physical activity (PA). Resting ankle-brachial index (ABI), the standard method for diagnosing PAD, has low sensitivity in the general population. Aim: To examine the association between PAD, identified using two definitions (ABI only and several different modalities), and accelerometry-derived PA in HCHS/SOL. Methods: Using interim data from 2,901 participants (mean age = 63 years; 67% female) from four U.S. sites, PAD was defined as (a) a resting ABI ≤0.90 or (b) if there was a significant drop in post-exercise ABI or at least 2 of the following conditions: 1) toe-brachial index ≤0.6, 2) abnormal Doppler waveforms, or 3) abnormal pulse-wave recordings. PA was measured 24 hours a day over 7 days using wrist-worn accelerometers and summarized as total activity counts/day (TAC), active time (min/day), and activity fragmentation (active-to-sedentary transition probability [ASTP], [higher=more fragmented]). We fitted linear regression models, adjusted for age, sex, smoking, adiposity, diabetes, and hypertension, and accounted for sampling weights. Results: PAD was identified in 104 participants (3.6%) by low resting ABI and 386 (13.3%) via the other modalities. When compared to those without PAD, those with an ABI ≤0.90 had lower and more fragmented daily PA (beta for TAC -227.9 [95% CI: -437.4, -18.4], active time -39.3 min [-76.5, -2.2], ASTP 1.8% [-0.2, 3.9]). Those with PAD identified by the other tests (vs. no PAD) also showed lower activity and more fragmented PA, but these associations were not statistically significant (Figure). Conclusion: PAD identified by a resting ABI ≤0.90 was significantly associated with lower and more fragmented PA, while PAD identified through other methods showed weaker associations with PA, suggesting that further research is needed to clarify how PAD with resting ABI >0.90 may affect PA.

Abstract P2058: Hypertension in Young Adults: Social Determinants and Control Using EHR Data

Introduction: Young adults are at risk for long-term cardiovascular complications if hypertension (HTN) remains unmanaged. There is limited exploration of how specific social determinants of health (SDoH), particularly in young adults, influence HTN control. Methods: HTN control was assessed among young adult patients (20 to 44 years) who completed SDoH screening in the Northwestern Medicine Health System. Exposures included 6 SDoH: no usual source of care, difficulty affording medication, mental health concerns, housing instability, transportation needs, and food insecurity. Sample included participants with SDoH measures and HTN as defined per 2017 ACC/AHA guidelines or ICD-10 code between 2018 and 2024 (N=36,377). Control was defined as blood pressure (BP) <140/<90 mmHg. Multivariable regression estimated the association between specific SDoH with HTN control, adjusted for age, sex, and race/ethnicity. Results: BP control at one year was 81.7% among hypertensive young adults. Hypertensive young adults with difficulty affording medication (OR 0.74; 95% CI 0.60-0.94; P=0.011) and housing instability (OR 0.63; 95% CI 0.43-0.96; P=0.027) were less likely to be controlled compared to those without these SDoH. Non-Hispanic Black young adults with HTN were less likely to be controlled compared to Non-Hispanic White young adults (OR 0.69; 95% CI 0.56-0.86; P<0.001). Hypertensive young adults on Medicaid were less likely to be controlled than those with a commercial health plan (OR 0.79; 95% CI 0.63-1.01; P=0.053). Conclusions: Improving medication accessibility and housing stability for young adults could improve HTN control. Future research should explore strategies to integrate SDoH screening into routine hypertension care.

An exploratory study of high-throughput transcriptomic analysis reveals novel mRNA biomarkers for acute myocardial infarction using integrated methods

Editorial Expression of Concern: ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy

Abstract MP58: Left ventricular hypertrophy among Black adults in a low-income country: the Haiti Cardiovascular Disease Cohort Study

Cardiovascular disease (CVD) is the leading cause of death globally and disproportionately affects low-and-middle income countries like Haiti. Left ventricular hypertrophy (LVH) is an important predictor of CVD incidence and mortality, but rarely measured in resource-constrained settings due to limited availability of echocardiograms (ECHO). Electrocardiograms (EKGs) may be a more accessible method to detect LVH. To address this gap, we determined the prevalence of LVH using echocardiography (LVH-ECHO), using EKGs (LVH-EKG), and compared diagnostic performance of EKGs versus ECHOs in detection of LVH in Haiti. We used enrollment data from the Haiti CVD Cohort study. Adults (≥18 years) living in Port-au-Prince were recruited using multistage random sampling between March 2019 and August 2021. All participants underwent standardized questionnaires to capture CVD risk factors, vital signs, physical exams, and EKGs. ECHOs were performed on participants with signs and symptoms of CVD or hypertension. Left ventricular mass was derived using 2D measurements with Devereux’s formula and indexed against body surface area (LVMI). LVH-ECHO was defined as LVMI >95 g/m 2 (female) and >115 g/m 2 (male), and defined by Sokolow-Lyon, Cornell Criteria and Limb-Lead Voltage criteria on EKGs. We compared risk factors for LVH-ECHO using univariate analysis and diagnostic performance of EKGs vs echocardiograms using sensitivity, specificity, likelihood ratio (LR) and accuracy. Among the 3,005 enrolled participants, 1,040 (34.6%) had both EKG and ECHO. Majority were female (67.0%) with mean age of 48.5 years (SD=15.3). Prevalence of LVH-ECHO was 39.0% (95%CI: 36.6%-41.5%), and associated with older age, having arrhythmia and lower education level attainment on univariate analysis. Prevalence of LVH-EKG ranged from 1.9%-5.0%. In comparing LVH-EKG to LVH-ECHO, all criteria had low sensitivity (<10%), high specificity (>90%) and moderate accuracy (62-64%). Limb-Lead voltage and Cornell criteria performed better in females (LR+ = 10.7) and males (LR+ = 8.2), respectively. Our findings show high prevalence of LVH-ECHO amongst a cohort of young Haitian adults with hypertension or CVD symptoms. All LVH-EKG criteria performed well on “ruling-in” LVH but missed cases of LVH due to poor sensitivity highlighting the need and capacity for ECHOs. Further research is needed to understand the utility of LVH diagnosis as a clinical tool to reduce CVD risk in low-resource settings.

Abstract P1034: Trends of Glucagon-Like Peptide 1 Receptor Agonist Usage, Self-Payments and Total Payments Among People Without Diabetes in the United States from 2017 -2022

Introduction: While originally developed for glucose lowering, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for weight loss. With the recent FDA approval of GLP-1 RAs for weight management in 2021 and broadening indications for use, trends of GLP-1 RA use, self-payment, and total associated payments among people without diabetes has important clinical and policy implications. Aim: We sought to describe trends of GLP-1 RA use, self-payments, and total associated payments among people without diabetes in the US from 2017 to 2022. Methods: We analyzed data from the Medical Expenditure Panel Survey (MEPS) from 2017-2022 for individuals without diabetes who reported use of GLP-1 RA. MEPS is conducted by the Agency for Healthcare Research and Quality and uses survey instruments to collect demographic, health, and economic information on a nationally representative noninstitutionalized US population. Prescription use and payments were determined by self-report and confirmed with respondent pharmacy. The total payment and out-of-pocket payment for GLP-1 RA were averaged per person for each data year. Results: A total of 148 participants representing 2,019,359 US adults without diabetes using GLP-1 RA were included. Mean (SD) age was 47.8 (14.7) years and 64.4% were female. The total weighted number of adults without diabetes who were prescribed GLP-1 RA increased 646% from 114,619 in 2017 to 854,728 in 2022 (p-value for trend < 0.01) with the greatest absolute increase between 2021-2022 ( Figure ). The average total payment increased from $2651 in 2017 to $6811 in 2022. The average self-payment decreased from $212 in 2017 to $157 in 2022. However, the changes were not statistically significant (p=0.3 for total payment; p=0.6 for self-payment). Conclusion: GLP-1 RA use among people without diabetes has increased significantly between 2017-2022 with the greatest absolute increase following FDA approval for weight management in 2021.

Abstract P2060: A pilot study of an intervention for self-management of blood pressure among refugees fleeing war and resettled in the United States

Introduction: Blood Pressure (BP) self-monitoring and medication self-titration can effectively mitigate disparities in hypertension control across populations. Refugees have a higher risk of uncontrolled hypertension, cardiovascular diseases (CVD) and other CVD risk factors. BP self-monitoring and medication self-titration have not been tested in refugees. Methods: We conducted a pilot intervention to assess the feasibility and preliminary efficacy of BP self-management through remote self-monitoring and hypothetical medication self-titration among Middle Eastern and North African (MENA) refugees in San Diego, California. Participants measured their BP at home three times per day, three days per week for four weeks. Data were collected via electronic surveys and electronic health records at baseline and after 4 weeks. We performed Chi-square tests and used Atlas.ti for qualitative thematic analyses. Results: Of 107 enrollees, 23 Syrians and 86 Iraqis, 53 (49%) were female. The mean age was 62 years (SD=9.8), and 66 (61%) had an annual household income of <$15,000. The average stay in the US was 9.7 years (SD=5.8), and 37 (35%) were able to read and write in English. The pilot intervention was successfully completed by 102 enrollees. At baseline, mean systolic blood pressure SBP was 128 mmHg (SD=16) and 36 individuals (34%) had uncontrolled BP (i.e., SBP ≥ 140 mm Hg). During the intervention, 91% of participants utilized the BP monitor >1 time/week, with week 1 having the highest utilization rate (97%) and week 4 having the lowest utilization rate (84%). For the index capturing intervention usability, functionality, and acceptability, participants scores averaged 80.7 (SD=15.8) showing a significant intervention preference. Lastly, (14%) of participants self-titrated BP medication based on SBP readings during the intervention, and (22%) correctly answered the hypothetical medication-titration question indicating the ability to follow the hypothetical medication-titration protocol. Qualitative analyses indicated a preference for provider-instructed medication titration, family support, and hypertension education to assist self-titration decisions. Conclusions: A large proportion of MENA refugees live in poverty and have uncontrolled BP. Self-monitoring is feasible, but medication self-titration remains a barrier in MENA refugees residing in San Diego. Results open doors for refugee-focused CVD health education efforts focused on medication self-titration.

Study of the hydrogeochemical processes and its impact on the quality of groundwater in the area between Abu Simbil and Tushka, Western Desert, Egypt

Abstract The study area is located in a hyper arid area in the Western Egyptian Desert, which represents a massive agricultural project where irrigation water is extracted from the Nubian sandstone aquifer. This study focuses on the hydrogeochemical processes and its impact on the quality of the groundwater aquifer. Based on the geomorphology, the study area includes five geomorphological units, Wadi Kurkur bediplain, Aswan High Dam Lake, the Nile Valley, the West Dungul plain, and basement outcrops. According to the geology, the study area is distinguished by sedimentary cover ranging in age from Upper Jurassic to Quaternary. Regarding the hydrogeology of the study area, the Nubian sandstone aquifer is the main aquifer in the study area, which it is represented by 24 groundwater samples plus one sample from the stem of the Lake Nasser. All samples were collected, analyzed, and interpreted. Groundwater salinity classification shows that all the groundwater samples are fresh water types, except one sample considered brackish water type. The pH values of the selected groundwater samples vary from 5.8 in the center to 7.6 in the northern side, with a median value of 7.3. The relationship between salinity content and the other ions shows a strong correlation between the values of Ca 2+ , Cl − , and SO 4 2− with the TDS values and a moderate correlation between Na + values with TDS values. Silicate and carbonate weathering are the main hydrochemical processes affecting the groundwater. From the saturation indices (SI) results, it is indicated that gypsum, anhydrite and manganite dissolve with negative SI values, whereas iron minerals are supersaturated with positive values. The hypothetical salts indicate a recharge from the lake Nasser in addition to leaching and dissolution of terrestrial salts. From the mixing Model, it is indicated that the Nubian sandstone aquifer has paleowater contribution percent ranging from 81 to 92% and Lake Nasser water contribution percent ranging from 7 to 18%. The nitrate concentrations are below the maximum allowable limits of the WHO; however, high concentrations of heavy metals were recorded in the groundwater samples at various extents.

SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation

Abstract MP33: Inflammatory proteomic signatures of metabolically unhealthy obesity

Background: Obesity is a risk factor for CVD incidence and mortality. Accumulating evidence implicates viscerally located adiposity may be particularly relevant for the progression of cardiovascular risk factors, with chronic inflammation as a plausible causal pathway. However, prior research has lacked precise phenotyping to characterize the relationship between visceral fat and inflammatory markers. Objective: Leveraging DXA body composition imaging and plasma proteomics measured by the Olink 384 inflammation panel, we aimed to (i) characterize phenotypes of metabolically glycemic unhealthy obesity and (ii) develop related novel inflammatory proteomic signatures ( i.e . “inflammotypes”). Methods: We analyzed 639 participants (mean age 63.7) from the VITamin D and OmegA-3 TriaL (VITAL) with DXA and proteomics at baseline. We defined four metabolic obesity phenotypes for each participant, as the sum of standardized values of visceral adipose tissue (VAT) mass and one of four glycemic metabolic traits, including fasting glucose, HbA1c, HOMA-IR, and LPIR (a lipid-based score predictive of incident diabetes). We also derived categorical phenotypes by cross-classifying VAT (high/low) with each glycemic trait (unhealthy/healthy), using cut-points that yielded the highest AUC. We then used elastic net regression models to identify the inflammotypes related to each of the four metabolic obesity phenotypes. Finally, we performed an external validation in the COcoa Supplement and Multivitamin Outcomes Study (COSMOS; N=371, mean age 69.0). Results: The continuous metabolic obesity measures were related to unique inflammotypes consisting of 86 to 102 proteins, with 21 proteins (including HGF, IL1RN, ISM1, PON3, and HSD11B1) shared across all phenotypes. For the categorical phenotypes, we identified 19, 22, and 3 proteins differentially expressed among metabolically unhealthy obesity subgroups, as defined for HbA1c, HOMA-IR, and LPIR metabolically unhealthy, respectively, but none were specific to fasting glucose. The inflammotypes were highly correlated with the corresponding phenotypes in COSMOS (Pearson correlation coefficients ranged from 0.63 to 0.82). Conclusion: We derived and externally validated novel proteomic inflammotypes of metabolically unhealthy obesity. These inflammotypes will be evaluated for the associations with subsequent risk of cardiometabolic outcomes in prospective longitudinal cohorts, to elucidate visceral adiposity-related pathways of CVD risk.